氢化可的松可降低用炭疽杆菌细胞壁肽聚糖攻击的大鼠的死亡率，并减少炎性细胞因子和一氧化氮的产生。
Hydrocortisone decreases lethality and inflammatory cytokine and nitric oxide production in rats challenged with B. anthracis cell wall peptidoglycan.
作者信息
Li Yan, Cui Xizhong, Shiloach Joseph, Wang Jeffrey, Suffredini Dante A, Xu Wanying, Liu Wancang, Fitz Yvonne, Sun Junfeng, Eichacker Peter Q
机构信息
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Building 10, Room 2C145, 10 Center Drive, Bethesda, MD, 20892, USA.
Biotechnology Core Laboratory, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
出版信息
Intensive Care Med Exp. 2020 Nov 18;8(1):67. doi: 10.1186/s40635-020-00358-4.
BACKGROUND
Lethal B. anthracis infection produces high proinflammatory peptidoglycan (PGN) burdens in hosts. We investigated whether the lethality and inflammation anthrax PGN can produce are related.
METHODS
At 6 h before and the start of 24 h anthrax PGN infusions, rats (n = 198) were treated with diluent (controls) or one of three IV-doses of either hydrocortisone (125, 12.5 or 1.25 mg/kg) or TNF-soluble receptor (TNFsr; 2000, 1000 or 333 μg/kg), non-selective and selective anti-inflammatory agents, respectively.
RESULTS
Compared to controls, hydrocortisone 125 and 12.5 mg/kg each decreased 7-day lethality (p ≤ 0.004). Hydrocortisone 125 mg/kg decreased IL-1β, IL-6, TNFα, MCP, MIP-1α, MIP-2, RANTES and nitric oxide (NO) blood levels at 4 and 24 h after starting PGN (except MCP at 24 h). Each decrease was significant at 4 h (except MIP-1α that was significant at 24 h) (p ≤ 0.05). Similarly, hydrocortisone 12.5 mg/kg decreased each measure at 4, 24 and 48 h (except TNFα at 24 h and MIP-1α at 24 and 48 h and NO at 48 h). Decreases were significant for IL-6 and NO at 4 h and RANTES at 48 h (p ≤ 0.05). Hydrocortisone 1.25 mg/kg had non-significant effects. Each TNFsr dose decreased lethality but non-significantly. However, when doses were analyzed together, TNFsr decreased lethality in a potential trend (p = 0.16) and IL-6 and NO significantly at 4 h (p = 0.05).
CONCLUSIONS
Peptidoglycan-stimulated host inflammation may contribute to B. anthracis lethality.
背景
致死性炭疽杆菌感染会使宿主产生高水平的促炎肽聚糖（PGN）。我们研究了炭疽杆菌PGN所导致的致死性与炎症之间是否存在关联。
方法
在注入炭疽杆菌PGN前6小时以及开始注入24小时期间，对198只大鼠进行处理，分别给予稀释剂（对照组）或三种静脉注射剂量之一的氢化可的松（125、12.5或1.25毫克/千克）或肿瘤坏死因子可溶性受体（TNFsr；2000、1000或333微克/千克），它们分别是非选择性和选择性抗炎剂。
结果
与对照组相比，125毫克/千克和12.5毫克/千克的氢化可的松均降低了7天致死率（p≤0.004）。125毫克/千克的氢化可的松在开始注入PGN后4小时和24小时降低了白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNFα）、单核细胞趋化蛋白（MCP）、巨噬细胞炎性蛋白-1α（MIP-1α）、巨噬细胞炎性蛋白-2（MIP-2）、调节激活正常T细胞表达和分泌因子（RANTES）以及一氧化氮（NO）的血液水平（24小时时的MCP除外）。在4小时时各项降低均显著（24小时时的MIP-1α除外）（p≤0.05）。同样，12.5毫克/千克的氢化可的松在4小时、24小时和48小时降低了各项指标（24小时时的TNFα、24小时和48小时时的MIP-1α以及48小时时的NO除外）。在4小时时IL-6和NO以及在48小时时RANTES的降低显著（p≤0.05）。1.25毫克/千克的氢化可的松作用不显著。各剂量的TNFsr均降低了致死率，但不显著。然而，当将各剂量一起分析时，TNFsr降低致死率呈潜在趋势（p = 0.16），并且在4小时时显著降低了IL-6和NO（p = 0.05）。
结论
肽聚糖刺激的宿主炎症可能导致炭疽杆菌致死。
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